Collagen Type II Fragment

Background: Plyometric exercise is used during rehabilitation after anterior cruciate ligament (ACL) reconstruction to facilitate the return to sports participation. However, clinical outcomes have not been examined, and high loads on the lower extremity could be detrimental to knee articular cartilage. Purpose: To compare the immediate effect of low- and high-intensity plyometric exercise during rehabilitation after ACL reconstruction on knee function, articular cartilage metabolism, and other clinically relevant measures. Study design: Randomized controlled trial; Level of evidence, 2. Methods: Twenty-four patients who underwent unilateral ACL reconstruction (mean, 14.3 weeks after surgery; range, 12.1-17.7 weeks) were assigned to 8 weeks (16 visits) of low- or high-intensity plyometric exercise consisting of running, jumping, and agility activities. Groups were distinguished by the expected magnitude of vertical ground-reaction forces. Testing was conducted before and after the intervention. Primary outcomes were self-reported knee function (International Knee Documentation Committee [IKDC] subjective knee form) and a biomarker of articular cartilage degradation (urine concentrations of crosslinked C-telopeptide fragments of type II collagen [uCTX-II]). Secondary outcomes included additional biomarkers of articular cartilage metabolism (urinary concentrations of the neoepitope of type II collagen cleavage at the C-terminal three-quarter-length fragment [uC2C], serum concentrations of the C-terminal propeptide of newly formed type II collagen [sCPII]) and inflammation (tumor necrosis factor-α), functional performance (maximal vertical jump and single-legged hop), knee impairments (anterior knee laxity, average knee pain intensity, normalized quadriceps strength, quadriceps symmetry index), and psychosocial status (kinesiophobia, knee activity self-efficacy, pain catastrophizing). The change in each measure was compared between groups. Values before and after the intervention were compared with the groups combined. Results: The groups did not significantly differ in the change of any primary or secondary outcome measure. Of interest, sCPII concentrations tended to change in opposite directions (mean ± SD: low-intensity group, 28.7 ± 185.5 ng/mL; high-intensity group, -200.6 ± 255.0 ng/mL; P = .097; Cohen d = 1.03). Across groups, significant changes after the intervention were increased the IKDC score, vertical jump height, normalized quadriceps strength, quadriceps symmetry index, and knee activity self-efficacy and decreased average knee pain intensity. Conclusion: No significant differences were detected between the low- and high-intensity plyometric exercise groups. Across both groups, plyometric exercise induced positive changes in knee function, knee impairments, and psychosocial status that would support the return to sports participation after ACL reconstruction. The effect of plyometric exercise intensity on articular cartilage requires further evaluation. Registration number: Clinicaltrials.gov NCT01851655.

To determine whether there is a direct correlation between the concentration of type II collagen fragment HELIX-II in synovial fluid and the severity of cartilage damage at the knee joint, 83 patients who had undergone knee arthroscopy or total knee replacement were enrolled in this study (49% women, mean ± SD age 49.5 ± 19). The content of HELIX-II in the synovial fluid samples was measured by enzyme-linked immunosorbent assay (ELISA). Cartilage damage at the knee joint was classified during arthroscopy or direct surgical observation, using the Outerbridge cartilage damage scoring system. The maximum damage score was defined as the highest score among the six areas of the knee joint, and the cumulative score was defined as the sum of the scores of the six areas of the knee joint. The intra-assay and inter-assay variations of the HELIX-II ELISA were lower than 13 and 15%, respectively. The level of HELIX-II in the severely damaged cartilage groups (cumulative scores = 11-24 or maximum score = 2-4) was much higher than in the slightly damaged cartilage groups (cumulative scores = 0-10 or maximum score = 0-1). The level of HELIX-II in cartilage from severely damaged cartilage groups was significantly higher than in the slightly damaged groups, but no significant difference was detected in the level of HELIX-II among the severely damaged cartilage sub-groups. There was a significant correlation between the HELIX-II concentration in the synovial fluid and the cumulative (r = 0.807) and maximum scores (r = 0.794). Thus, elevated HELIX-II level is correlated with early cartilage lesions, but does not have the sensitivity to predict the progression of severity of cartilage damage in the knee joint.

The urinary C-terminal telopeptide fragment of type II collagen (uCTX-II) has been reported as the efficient blood-based biomarker for osteoarthritis, which affects knees, hands, spine, and hips. This study reports a sensing strategy with antibody-conjugated gold nanoparticles (GNP) on an interdigitated electrode (IDE) to determine uCTX-II. The GNP-antibody complex was chemically immobilized on the IDE surface through the amine linker. uCTX-II was determined by monitoring the alteration in current upon interacting the GNP-complexed antibody. This strategy was improved the detection by attracting higher uCTX-II molecules, and the detection limit falls in the range of 10-100 pM with an acceptable regression value [y = 0.6254x - 0.4073, R² = 0.9787]. The sensitivity of the detection was recognized at 10 pM. Additionally, upon increasing the uCTX-II concentration, the current changes were increased in a linear fashion. Control detection with nonimmune antibody and control protein do not increase the current level, confirming the specific detection of uCTX-II. This method of detection helps in diagnosing osteoarthritis and its follow-up treatment.